The basis of schizophrenia and affective disorders remains unknown. Although a genetic component is likely, discordance for disease in monozygotic twin studies and epidemiology suggest the presence of cofactors. One candidate risk factor is brain infection. Although no linkage has been established between any infectious agent and either affective disorders or schizophrenia, a potential role in their pathogenesis has been suggested for Borna disease virus (BDV). BDV is a neurotropic RNA virus, worldwide in distribution, that causes movement and behavior disturbances in warmblooded animal hosts ranging from birds to primates. It is not lytic in vitro or in vivo, replicates at lower levels than most known viruses and is dissimilar in nucleic acid and protein sequence to other infectious agents. Sensitive, specific methods for detection of BDV infection were established only recently. Based on serology and RT-PCR analysis of peripheral blood mononuclear cells (PBMC), groups in North America, Europe and Asia have reported evidence of BDV infection in patients with affective disorders and schizophrenia as well as in domesticated animals that could serve as vectors for virus transmission. The prevalence estimates of BDV infection in patients and controls differ between research groups. To date there has been no blinded multicenter analysis of sera and PBMC samples from well characterized patients and controls using standardized methods for diagnosis of psychiatric illness and BDV infection. Thus, the significance of BDV for pathogenesis of neuropsychiatric disease remains controversial. Four clinical centers and a core laboratory will join in a united effort to rigorously address the epidemiology of BDV in human populations. Specific aims will be: (1) establish a multicenter group to investigate potential linkages between Borna disease virus infection and neuropsychiatric disease; (2) determine the prevalence of serum antibodies to Borna disease virus proteins in subjects with schizophrenia, affective disorders, and normal controls; and (3) determine the prevalence of Borna disease virus nucleic acids in PBMC of subjects with schizophrenia, affective disorders, and normal controls. Interpretation of previous RT-PCR analyses of human materials was complex because samples were processed in laboratories working with other BDV isolates and putative human sequences were sufficiently similar to known isolates that contamination could not be excluded. This study will be the first to collect and process human sera and PBMC samples in clinical laboratories with no history of BDV research and dispense aliquots to a central laboratory for randomized, blinded analysis.